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04/28/17 09:30

28.04.2017 – Important cellular and molecular mechanisms of bone marrow fibrosis in hematopoietic malignancies discovered

Bone marrow (BM) fibrosis is a fatal disorder in which normal bone marrow tissue and blood-forming cells are gradually replaced with thick coarse fibers and scar-like tissue. Over time, this leads to failure of the body to produce blood cells and ultimately to death. The specific mechanisms that cause BM fibrosis are not understood, in particular, as the cells driving fibrosis have remained obscure. The laboratories of Rafael Kramann (Division of Nephrology and Clinical Immunology, Uniklinik RWTH Aachen) and Rebekka Schneider (Division of Hematology and Oncology, Uniklinik RWTH Aachen and Department of Hematology, Erasmus Medical School, Rotterdam) and their collaboration partners have now revealed the cellular origin of BM fibrosis.

In their work published today in Cell Stem Cell (http://www.cell.com/action/showMethods?pii=S1934-5909(17)30079-6), they demonstrate that Gli1 marks a subset of bone marrow stromal cells that turn into scar forming myofibroblasts upon exposure to malignant hematopoietic stem cells. Importantly, the authors show that genetic ablation or pharmacologic targeting of these cells by Gli protein inhibition abolishes bone marrow scar formation (fibrosis) and rescues bone marrow failure (anemia) in mice. Furthermore, the authors demonstrate that the same pathway is active in human disease where Gli1 expression correlates with disease severity. Therefore, Gli inhibition might be a promising novel therapeutic strategy. This work has important implications for both better understanding of the disease, for improved diagnostics and for improved treatments, as bone marrow fibrosis is regarded as an incurable disease.

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